title: Exonic deletion of CASP10 in a patient presenting with systemic juvenile idiopathic arthritis, but not with autoimmune lymphoproliferative syndrome type IIa.
abstract: Systemic juvenile idiopathic arthritis (s-JIA) is a rare inflammatory disease classified as a subtype of chronic childhood arthritis, manifested by spiking fever, erythematous skin rash, pericarditis and hepatosplenomegaly. The genetic background underlying s-JIA remains poorly defined. To detect copy number variations, we performed single nucleotide polymorphism (SNP) array analysis in 50 patients with s-JIA. We found a 13-kb intragenic deletion of CASP10 in one patient. RT-PCR of the mRNA extracted from the patient's lymphoblastoid cells revealed that CASP10 mRNA was truncated. Sequencing the mRNA revealed that this deletion resulted in a frame shift with an early stop codon. CASP10 is known as a causative gene for autoimmune lymphoproliferative syndrome (ALPS) type IIa, another childhood syndrome of lymphadenopathy and splenomegaly associated with autoimmune haemolytic anaemia and thrombocytopenia. TCR αβ(+) CD4/CD8 double-negative T cells in the peripheral blood as a diagnostic marker of ALPS were not high in this patient and lymphocyte apoptosis induced by anti-Fas antibody was normal, denying ALPS in the patient. The father and a sister of the patient showing no symptoms of ALPS or s-JIA, also had the same deletion. Furthermore, we found no other mutations of CASP10 in the other 49 s-JIA patients. These data suggest that the pathogenic significance of CASP10 mutations should be carefully evaluated in s-JIA or even ALPS type IIa in further studies.
authors.affiliation: Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan Department of Pediatrics, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Tadaki
authors.forename: H
authors.initials: H
authors.lastname: Saitsu
authors.forename: H
authors.initials: H
authors.lastname: Kanegane
authors.forename: N
authors.initials: N
authors.lastname: Miyake
authors.forename: T
authors.initials: T
authors.lastname: Imagawa
authors.forename: M
authors.initials: M
authors.lastname: Kikuchi
authors.forename: R
authors.initials: R
authors.lastname: Hara
authors.forename: U
authors.initials: U
authors.lastname: Kaneko
authors.forename: T
authors.initials: T
authors.lastname: Kishi
authors.forename: T
authors.initials: T
authors.lastname: Miyamae
authors.forename: A
authors.initials: A
authors.lastname: Nishimura
authors.forename: H
authors.initials: H
authors.lastname: Doi
authors.forename: Y
authors.initials: Y
authors.lastname: Tsurusaki
authors.forename: H
authors.initials: H
authors.lastname: Sakai
authors.forename: S
authors.initials: S
authors.lastname: Yokota
authors.forename: N
authors.initials: N
authors.lastname: Matsumoto
mesh_terms: D001171:Arthritis, Juvenile / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D001483:Base Sequence; D053455:Caspase 10 / Q000235:genetics*; D053181:Caspase 8 / Q000235:genetics; D002648:Child; D002889:Chromosomes, Human, Pair 2; D005091:Exons / Q000235:genetics*; D005260:Female; D023061:Gene Order; D055106:Genome-Wide Association Study; D006801:Humans; D008969:Molecular Sequence Data; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D016415:Sequence Alignment; D017384:Sequence Deletion / Q000235:genetics*; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism
chemical_list: D053455:Caspase 10; D053181:Caspase 8